Kalafungin, grantican B and the nanaomycins are members of a growing family of naturally occurring antibiotics containing quinones fused to a pyrano-gamma-lactone moiety. Clinical testing has shown kalafungin to be inhibitory in vitro against a variety of pathogenic fungi, yeasts, protozoa and gram positive and gram negative bacteria. To date, no synthetic approaches to this interesting class of natural products have appeared.
This invention has as its primary objective an overall synthesis route for this class of antibiotic compounds. In addition, a new and novel antibiotic compound, which is not naturally occurring, 9-deoxykalafungin, has been prepared. And tests show this compound to exhibit, in some instances, superiority in terms of inhibitory effect when compared to naturally occurring kalafungin.
Accordingly, one object of the invention is to prepare via synthetic approaches, an interesting class of natural products by construction of the basic ring system of the quinone pyrano-gamma-lactone antibiotics in a short, efficient synthesis route.
Yet another object of this invention is to prepare such compounds as mentioned above at yield levels which are economically feasible for mass production.
A still further object is to prepare 9-Deoxykalafungin.
The method and manner of accomplishing each of these stated objectives will become apparent from the detailed description of the invention which follows.